Traditionally, it was common practice to implant arterial or venous cannulas in larger mammals, such as dogs. These animals were then often used for repeated administrations of predetermined amounts of drugs. More recently, aorta and right ventricle catheterization of rats and ground squirrels has permitted direct measurements of blood pressures and drug absorption without the errors associated with anesthesia and restrainment. V. Popovic et al., Permanent Cannulation of Aorta and Vena Cava in Rats and Ground Souirrels. J. Appl. Physiol. 15: 727-728, 1960; V. Popovic et al., Technicue of Permanent Cannulation of the Right Ventricle in Rats and Ground Squirrels. Proc. Soc. Exptl. Biol. Med. 113: 599-602, 1963.
Despite these advances, the mouse, a commonly used experimental animal, has been considered too small for permanent catheterization. The small body size of these animals has generally limited blood sampling to nonsurgical methods. With acute terminal procedures, decapitation and trunk blood collection or cardiac puncture are often used. Other situations, however, require multiple sequential blood samples from the same mouse. The easiest and most common techniques involve collection from the caudal blood vessels in the tail. Following immobilization of the mouse, these vessels are either transected, lanced, or punctured to produce hemorrhage. The other common multiple sampling method is retro-orbital membrane puncture and collection from the ophthalmic venous plexus. This is generally considered the preferred nonsurgical approach for repetitive blood sampling in the mouse. However, this approach has drawbacks which include the unavoidable stress of physical or chemical restraint, the potential for excessive trauma and the human psychological discomfort associated with learning and using this technique.
One attempt to provide catheterization to unanesthetized mice is disclosed in P. Popovic et al, Permanent Cannulation of Blood Vessels in Mice. J. Appl. Physiol. vol. 25, No. 5, pp. 626, 627 (November, 1968). This article is directed to a technique and apparatus for permanent cannulation for mice using small polyethylene tubings. The cannula of this invention is intended to be disposed in a jugular vein or carotid artery for use in cardiovascular studies or the administration of drugs into the blood stream of the animals. This reference, however, lacks a teaching for a fully mobile catheterization apparatus for reducing stress distortion of blood parameters caused by "leashing" these animals to a limited circular area. While this short length prevents damage from chewing, the mouse must be subjected to the stress of almost full immobilization whenever the catheter is used.
Another mouse cannula is taught by A. Coquelin er al, Secretion of Luteinizing Hormone in Male Mice: Factors that Influence Release During Sexual Encounters, Edocrinology, vol. 106, pp. 1224, 1229 (1980). This discussion is direcred to a study for measuring the sequential changes in blood levels of luteinizing hormone during sexual encounters and discloses a chronic cannulation procedure and catheter. The catheter employs a polyethylene stopper which is sutured to the mouse's back. Also included is a swivel means for supporting the entire unit from above and a flare-type tubing adaptor which is soldered to an extension spring that holds the tubing material of the catheter. Although this reference discloses a catheterization apparatus for use in small mammals, such as mice, it also does not disclose a fully mobile device for minimizing stress.
Although, not directed to mouse catheter devices, H. Raffe et al, Measurement of Hormones and Blood Gases During Hypoxia in Conscious Cannulated Rats, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 56 (5), pp. 1426-1430, 1984, teaches apparatus and methods for implanting chronic arterial cannulas for remote stress-free blood-sampling of conscious unrestrained rats in their own cages. The references discloses the use of lengths of stainless steel spring coils for sheathing the cannulas from the rat to the top of the cage. In addition to these sheaths, the use of quinidine sulfate is disclosed to discourage chewing. The cannula of this reference employs polyethylene tubing of various sizes and subcutaneously implanted stainless steel discs, having a central hollow stem for receiving part of the spring coil. These discs also include a set screw and four suture holes. This reference, however, also fails to disclose a fully mobile in-dwelling catheterization apparatus suited for mice.
Similarly, A. K. Chatham, Jacket and Swivel and Teathering Systems. Lab Animal, vol. 14 (8), pp. 29-33, 1985, is directed to restraining devices for larger animals that may include exteriorized catheters and probes for infusing drugs and collecting data. The tethering system consists of a jacket made of a light weight breathable nylon netting material, a light weight, highly flexible stainless steel attaching tether, and a cage-mounted swivel to which the tether is anchored. This reference discloses jacket and swivel tethering systems for use on a variety of research animals, as small as 150 grams, or about five times the weight of an average mouse. As shown in FIG. 3 of this reference, the freedom of movement for the animal is determined by the length of the tether and a fully mobile catheterization apparatus is not disclosed.
Accordingly, there is still a need for a swivel tethering device for use in scientific studies of laboratory animals. There is also a need for a fully mobile catheterization apparatus for obtaining serial blood samples from nonrestrained and unanesthetized mice without the stress associated with confinement to a given tether length.